1. Field of the Invention
The present invention relates to a method for the treatment of head and neck cancer.
2. Background Art
In the United States, 50,000 people are diagnosed with head and neck cancers per year, and about 60% of them fall into locally advanced stage III/IV cases. Head and neck tumors exhibit a variety of tissue types, and 80% or more of the cases are classified as squamous cell carcinomas. Therefore, treatment methods heretofore developed have focused primarily on squamous cell carcinomas. The head and neck section is an assembly of a plurality of organs, and the primary foci of head and neck cancer include the paranasal sinus, the epipharynx, the oropharynx, the oral cavity, the hypopharynx, the larynx, and the salivary glands. The prognosis of the head and neck cancer varies, depending on the primary focus thereof. Among head and neck cancers, the prognosis is the worst in hypopharynx cancer and the most favorable in epipharynx cancer. In particular, locally advanced head and neck cancer exhibits a poor prognosis, and a five-year survival rate is reported as 20 to 50%.
A variety of methods are available for the treatment of head and neck cancer, including surgical resection, radiotherapy, chemoradiotherapy, and chemotherapy, which are selected in accordance with the stage and affected site. Generally, when the cancer is resectable, surgical resection is used as a standard method. If the cancer is in an early stage, radiotherapy or a similar treatment is performed. Recently, there are many patients who want to maintain function of an organ such as the larynx and therefore, radiotherapy and chemotherapy have been used in combination in order to attain higher local controllability. When a patient desires to conserve the larynx, chemoradiotherapy is conceived to be a standard treatment, on the basis of randomized trial results comparing chemoradiotherapy with radiation therapy alone. Meanwhile, radiotherapy has conventionally been applied to locally advanced head and neck cancer, to which radical resection cannot be applied. However, the treatment results are unsatisfactory. Randomized trial results comparing chemoradiotherapy with radiation therapy alone show that chemoradiotherapy exhibits considerably higher local controllability and survival rate and thus is conceived to be a standard treatment for unresectable head and neck cancer, although potentiation of toxicity to the bone marrow and the digestive system (e.g., mucositis) is observed. Thus, regardless of whether the cancer is resectable, chemoradiotherapy is widely applied to locally advanced head and neck cancers (see Non-Patent Documents 1 to 9).
Heretofore, a variety of anti-cancer agents have been used in combination with radiotherapy. However, a standard regimen in terms of the anti-cancer agent to be combined, the dose and way of administration, administration schedule, etc. which is to be used with radiotherapy has not yet been established. From early 1980's, combination chemotherapies which generally use cisplatin (CDDP) have been developed in the U.S. and Europe, and the FP therapy (i.e., combination chemotherapy using 5-fluorouracil (5-FU) and cisplatin) has been reported to exhibit a high antitumor effect with a response rate of 88% and a CR rate of 19%, with respect to locally advanced head and neck cancer (Non-Patent Document 10). Since then, the FP therapy has been recognized to be the most effective regimen for locally advanced head and neck cancer, and has been widely used in combination with radiotherapy. In a meta-analysis carried out by Browman and others, regimens using platinum-based drugs such as cisplatin, Mitomycin C, 5-FU, and Bleomycin, respectively, exhibit odds ratios of 0.57 (95% CI, 0.46-0.71; p<0.00001), 0.54 (95% CI, 0.30-0.95; p=0.032), 0.66 (95% CI, 0.39-1.10; p=0.11), and 0.80 (95% CI, 0.50-1.29; p=0.36), indicating that the regimen using a platinum-based drugs exhibits the highest add-on effect on survival (see Non-Patent Document 9). Furthermore, although use of an anti-cancer agent alone and combination chemotherapy exhibit odds ratios of 0.63 (95% CI, 0.48-0.81; p=0.0004) and 0.63 (95% CI, 0.48-0.83, p=0.0009), respectively, which are equal to each other, the FP therapy exhibits an odds ratio of 0.53 (95% CI, 0.41-0.69; p<0.00001), indicating that this therapy promises the highest add-on effect on survival. As described hereinabove, a platinum-based drug such as cisplatin has been recognized as a key drug to locally advanced head and neck cancer, and for this, cisplatine alone or the FP therapy is widely used.
Use of S-1 alone (80 mg/m2/day, four-week administration, followed by two-week rest) exhibits response rate of 34.1% (29/85) with respect to advanced/relapsed head and neck cancer, and a percent efficacy of 30.4% (21/69) with respect to the relapse cases in which treatment using radiotherapy, combination chemotherapy (e.g., a platinum-based drug and a 5-FU-based anti-malignant-tumor agent), etc. has already been performed. The response rate is higher than 15%, which is the response rate obtained through use of a 5-FU drug alone (continuous intravenous infusion) (see Non-Patent Documents 11). A combination chemotherapy (S-1 and cisplatin) has been extensively used with advanced/relapsed gastric cancer (see, for example, Non-Patent Documents 12 and 13), and some cases of applying such a therapy to head and neck cancer have also been reported recently (see, for example, Non-Patent Document 14 to 20). For example, Fujii and others carried out a phase I/II trial of an S-1+CDDP therapy with respect to relapsed/advanced head and neck cancer. In the trial, 38 patients in total were tested, and excellent antitumor effect was attained with a best response of 67.6% (23/34) and a confirmed response of 44.1% (15/34). In this trial, toxicities of grade 3 or higher were found to be expressed as follows: neutropenia 11.8%, anemia 8.8%, thrombocytopenia 11.8%, anorexia 26.5%, nausea 14.7%, fatigue 8.8%, and diarrhea 2.9% (see Non-Patent Document 20).
Non-Patent Document 1:
    Marcial V A, Pajak T F. Radiation therapy alone or in combination with surgery in head and neck cancer. Cancer 1985; 55(9 Suppl): 2259-65.Non-Patent Document 2:    Adelstein D J, Li Y, Adams G L, et al. An intergroup phase III comparison of standard radiation therapy and two schedules of concurrent chemoradiotherapy in patients with unresectable squamous cell head and neck cancer. J Clin Oncol 2003; 21(1): 92-8.Non-Patent Document 3:    Brizel D M, Albers M E, Fisher S R, et al. Hyperfractionated irradiation with or without concurrent chemotherapy for locally advanced head and neck cancer. N Engl J Med 1998; 338(25): 1798-804.Non-Patent Document 4:    Merlano M, Benasso M, Corvo R, et al. Five-year update of a randomized trial of alternating radiotherapy and chemotherapy compared with radiotherapy alone in treatment of unresectable squamous cell carcinoma of the head and neck. J Natl Cancer Inst 1996; 88(9): 583-9.Non-Patent Document 5:    20. Zakotnik B, Smid L, Budihna M, et al. Concomitant radiotherapy with mitomycin C and bleomycin compared with radiotherapy alone in inoperable head and neck cancer: final report. Int J Radiat Oncol Biol Phys 1998; 41(5): 1121-7.Non-Patent Document 6:    Adelstein D J, Lavertu P, Saxton J P, et al. Mature results of a phase III randomized trial comparing concurrent chemoradiotherapy with radiation therapy alone in patients with stage III and IV squamous cell carcinoma of the head and neck. Cancer 2000; 88(4): 876-83.Non-Patent Document 7:    Wendt T G, Grabenbauer G G, Rodel C M, et al. Simultaneous radiochemotherapy versus radiotherapy alone in advanced head and neck cancer: a randomized multicenter study. J Clin Oncol 1998; 16(4): 1318-24.Non-Patent Document 8:    Pignon J P, Bourhis J, Domenge C, Designe L. Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-Analysis of Chemotherapy on Head and Neck Cancer. Lancet 2000; 355(9208): 949-55.Non-Patent Document 9:    Browman G P, Hodson D I, Mackenzie R J, Bestic N, Zuraw L. Choosing a concomitant chemotherapy and radiotherapy regimen for squamous cell head and neck cancer: A systematic review of the published literature with subgroup analysis. Head Neck 2001; 23(7): 579-89.Non-Patent Document 10:    Kish J, Drelichman A, Jacobs J, et al. Clinical trial of cisplatin and 5-FU infusion as initial treatment for advanced squamous cell carcinoma of the head and neck. Cancer Treat Rep 1982; 66(3): 471-4.Non-Patent Document 11:    Inuyama Y, Kida A, Tsukuda M, Kohno N, Satake B. [Late phase II study of S-1 in patients with advanced head and neck cancer]. Gan To Kagaku Ryoho 2001; 28(10): 1381-90.Non-Patent Document 12:    Takahashi T, Saikawa Y, et al. Histological Complete Response in a Case of Advanced Gastric Cancer Treated by Chemotherapy with S-1 Plus Low-dose Cisplatin and Radiation. Jpn. J. Clin. Oncol., 2003; 33(11); 584-588Non-Patent Document 13:    Iwase H, Indo T, et al. Esophageal cancer with colonic metastasis successfully treated by chemoradiotherapy followed by chemotherapy with S-1 and cisplatin. Int. J. Clin. Oncol., 2004; 9; 394-402Non-Patent Document 14:    Japanese Journal of Cancer and Chemotherapy, 30(12), p1945-1947, 2003.11Non-Patent Document 15:    Japanese Journal of Cancer and Chemotherapy, 30(4), p511-515, 2003.4Non-Patent Document 16:    Japanese Journal of Cancer and Chemotherapy, 30(9), p1309-1312, 2003.9Non-Patent Document 17:    Japanese Journal of Cancer and Chemotherapy, 31(2), p215-217, 2004.2Non-Patent Document 18:    Head and Neck Cancer, 30(2), p282(2004).Non-Patent Document 19:    Harada K, Kawaguchi S, Supriatno, Onoue T, Yoshida H, Sato M. Combined effects of the oral fluoropyrimidine anticancer agent, S-1 and radiation on human oral cancer cells. Oral Oncol 2004; 40(7): 713-9.Non-Patent Document 20:    M. Fujii, S. Endo, et al., A Phase I/II study of S-1 plus Cisplatin (CDDP) in Patients with Head and Neck Cancer (HNC). Proc. ASCO 24: 513 (abstr 5552), 2005.
However, even when the aforementioned anti-cancer drugs are used in combination or concurrently with radiotherapy, the treatment efficacy to advanced head and neck cancer is unsatisfactory. Thus, demand has arisen for a new treatment method. Furthermore, it is generally very difficult to predict whether or not a treatment method which has been effective for a certain cancer type is also effective with respect to other types of cancer. Therefore, the timing of combination of radiotherapy with chemotherapy and selection of the type of chemotherapy are determined only on the basis of actual clinical data.